Fast fluid-attenuated inversion-recovery (FLAIR) sequences are sensitive for detecting lesions in... more Fast fluid-attenuated inversion-recovery (FLAIR) sequences are sensitive for detecting lesions in patients with multiple sclerosis (MS). More rapid fast-FLAIR imaging of the brain can be achieved by the concomitant use of half-Fourier acquisition single-shot turbo spin-echo (HASTE-FLAIR) and echo-planar imaging (EPI-FLAIR). The present study was performed in a large cohort of subjects to assess and compare the number and volume of brain lesions detected by the fast-FLAIR, HASTE-FLAIR, and EPI-FLAIR sequences in patients with MS. Fast-FLAIR, HASTE-FLAIR, and EPI-FLAIR sequences were obtained from 46 consecutive MS patients. Lesions seen on each type of sequence were counted and classified by consensus by two observers. Lesion volumes were measured using a semiautomated segmentation technique based on local thresholding. The quality of the fast-FLAIR images was significantly better than that of HASTE-FLAIR and EPI-FLAIR images. Fast-FLAIR revealed significantly more lesions and higher...
Neuroborreliosis is frequently indistinguishable from multiple sclerosis (MS) on both clinical an... more Neuroborreliosis is frequently indistinguishable from multiple sclerosis (MS) on both clinical and radiologic grounds. By using MR imaging, we assessed "occult" brain white matter (WM), brain gray matter (GM), and cervical cord damage in patients with neuroborreliosis in an attempt to achieve a more accurate picture of tissue damage in these patients, which might contribute to the diagnostic work-up. We studied 20 patients with neuroborreliosis and 11 sex- and age-matched control subjects. In all subjects, we acquired dual echo, T1-weighted, diffusion tensor (DT) and magnetization transfer (MT) MR imaging scans of the brain and fast short-tau inversion recovery and MT MR imaging scans of the cervical cord. T2-visible lesion load was measured by using a local thresholding segmentation technique. Mean diffusivity and fractional anisotropy histograms of the brain and cervical cord MT ratio histograms were produced. Normalized brain volumes (NBV) were measured by using SIENAx....
Improving the sensitivity of MR imaging for the detection of multiple sclerosis (MS) lesions in t... more Improving the sensitivity of MR imaging for the detection of multiple sclerosis (MS) lesions in the cord might be useful in the diagnostic workup and could lead to a better understanding of the evolution of the disease. The purpose of this study was to compare fast spin-echo (FSE) with magnetization transfer-prepared gradient-echo (MT-GE) and fast short-inversion-time inversion recovery (fast-STIR) MR sequences to determine which is best for imaging cervical cord lesions in MS patients. FSE, MT-GE, and fast-STIR MR images were obtained in 56 MS patients and 10 healthy control subjects with a 1.5-T MR system and a phased-array coil. Cord lesions seen on images obtained with each sequence were counted by two observers in two stages (stage 1: random review of the complete sets of images from each technique; stage 2: side-by-side review with a retrospective count of lesions). At the end of stage 1, a mean of 1.16 cord lesions per patient were seen on FSE images, 1.57 on MT-GE images (35...
We describe the dynamics and the nature of the presymptomatic phase of multiple sclerosis (MS) in... more We describe the dynamics and the nature of the presymptomatic phase of multiple sclerosis (MS) in a patient for whom MR abnormalities suggestive of MS were found before the development of clinical symptoms. The patient was monitored with serial monthly MR imaging of the brain and spinal cord for 5 months. Disease activity during the presymptomatic phase showed imaging characteristics comparable to that of early relapsing-remitting MS in terms of enhancing lesions, duration of enhancement, and new lesions depicted by T2-weighted imaging. Measurements derived from magnetization transfer imaging suggested that the amount and degree of tissue destruction within and outside the lesions revealed by T2-weighted imaging were mild. This, together with the fact that only one of the 43 new lesions that developed during the presymptomatic phase was located in a neurologically eloquent area, may be the reason why, for a relatively long period, the patient had no clinical manifestations of MS des...
Hypointense lesions can be visible on fast fluid-attenuated inversion recovery (FLAIR) MR images ... more Hypointense lesions can be visible on fast fluid-attenuated inversion recovery (FLAIR) MR images of the brain of patients with multiple sclerosis (MS), and they may be produced by severely damaged white matter. To test the role of these lesions as an MR marker of MS severity, we assessed their relationship with clinical findings and other MR measures. Using a 1.5-T scanner, dual-echo rapid acquisition with relaxation enhancement, fast FLAIR, and T1-weighted MR images (24 axial, 5-mm-thick contiguous interleaved sections) were obtained from 50 patients (32 with relapsing-remitting and 18 with secondary progressive MS). Hypointense lesions were visible on the fast FLAIR images of 19 patients (mean number of lesions, 7.8; range 1-22); their median load was 1.4 mL (range, 0.05-12.6 mL). The median lesion load was significantly higher in patients with secondary progressive MS than in those with relapsing-remitting MS on the T1-weighted images. Both the number and the load of hypointense ...
MR imaging is now widely used to monitor disease progression in patients with multiple sclerosis ... more MR imaging is now widely used to monitor disease progression in patients with multiple sclerosis (MS). The purpose of this study was to explore the relationship between disability status and existing and new MR parameters in MS patients. Forty-one patients with clinically definitive MS were studied. MR imaging included T2- and T1-weighted imaging as well as gradient-echo imaging with and without magnetization transfer contrast. We used surface-based thresholding segmentation techniques to obtain T2 and T1 lesion load, T1/T2 ratio, and several magnetization transfer ratio (MTR) lesion load parameters. MTR histographic analysis included measurements of absolute peak height (aHp), relative peak height (rHp), MTR of the peak (MTRp), mean MTR (MTRm), and MTR25, MTR50, and MTR75, relating to the integrals of the histogram at 25%, 50%, and 75%, respectively, of the total area under the curve. All MR parameters were correlated with Expanded Disability Status Scale (EDSS) score, disease dura...
Our goal was to evaluate whether improved spatial resolution of MR images results in the detectio... more Our goal was to evaluate whether improved spatial resolution of MR images results in the detection of higher volumes of hypointense lesions in patients with multiple sclerosis (MS). A magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) sequence with subsequent reconstruction of axial sections with 5-, 3-, and 1-mm thickness and a dual-echo sequence were obtained in 16 patients with relapsing-remitting or secondary-progressive MS. The volumes of MR imaging abnormalities present on each of these studies were measured using a semiautomated segmentation technique based on local thresholding. The hypointense lesion volumes seen on the three reconstructed MP-RAGE sets of images were compared using the Friedman test and correlated with the hyperintense lesion volume on proton density-weighted images and with scores on the Expanded Disability Status Scale using Spearman's rank correlation coefficient. The median volume of hypointense lesions increased from 1.2 mL (range, 0 ...
We describe a case of hereditary congenital mirror movements (MMs) in a 76-year-old man, who afte... more We describe a case of hereditary congenital mirror movements (MMs) in a 76-year-old man, who after an ischemic stroke, had persistence of MMs in the paretic hand during voluntary movements of the contralateral arm. By using functional MR imaging to investigate the performance of motor and sensory tasks with the affected and the unaffected hands, we found evidence for increased ipsilateral primary motor cortex activity and reduced transcallosal inhibition. Both these mechanisms are likely to be involved in the genesis of MMs.
The spinal cord is frequently involved in multiple sclerosis (MS), and cord damage may be an impo... more The spinal cord is frequently involved in multiple sclerosis (MS), and cord damage may be an important contributor to disability. Diffusion tensor magnetic resonance imaging (DT-MRI) provides quantitative information about the structural and orientational features of the central nervous system. In order to assess whether diffusion tensor-derived measures of cord tissue damage are related to clinical disability, mean diffusivity (MD) and fractional anisotropy (FA) histograms from the cervical cord were acquired from a large cohort of MS patients. Diffusion-weighted sensitivity-encoded (SENSE) echo planar images of the cervical cord, and brain dual-echo and diffusion-weighted scans were acquired from 44 patients with MS and 17 healthy controls. Cord and brain MD and FA histograms were produced. An analysis of variance model, adjusting for cord volume and patient age, was used to compare cord DT-MRI parameters from controls and patients. A multivariate linear regression model was used to identify DT-MRI variables independently associated with disability. Average cervical cord FA was significantly lower in MS patients compared to controls. Cord cross-sectional area, average FA and average MD were all significantly correlated with the degree of disability (r values ranging from 0.36 to 0.51). The multivariate linear regression model retained average cord FA and average brain MD as variables independently associated with disability, with a correlation coefficient of 0.73 (P < 0.001). DT-MRI reveals a loss of cervical cord tissue structure in MS patients. The strong correlation found between a composite DT-MRI score and disability suggests that a full and accurate assessment of cervical cord damage in MS provides information that usefully contributes to an explanation of the clinical manifestations of the disease.
Objective: Based on the theories of brain reserve and cognitive reserve, we investigated whether ... more Objective: Based on the theories of brain reserve and cognitive reserve, we investigated whether larger maximal lifetime brain growth (MLBG) and/or greater lifetime intellectual enrichment protect against cognitive decline over time. Methods: Forty patients with multiple sclerosis (MS) underwent baseline and 4.5-year follow-up evaluations of cognitive efficiency (Symbol Digit Modalities Test, Paced Auditory Serial Addition Task) and memory (Selective Reminding Test, Spatial Recall Test). Baseline and follow-up MRIs quantified disease progression: percentage brain volume change (cerebral atrophy), percentage change in T2 lesion volume. MLBG (brain reserve) was estimated with intracranial volume; intellectual enrichment (cognitive reserve) was estimated with vocabulary. We performed repeatedmeasures analyses of covariance to investigate whether larger MLBG and/or greater intellectual enrichment moderate/attenuate cognitive decline over time, controlling for disease progression. Results: Patients with MS declined in cognitive efficiency and memory (p , 0.001). MLBG moderated decline in cognitive efficiency (p 5 0.031, h p 2 5 0.122), with larger MLBG protecting against decline. MLBG did not moderate memory decline (p 5 0.234, h p 2 5 0.039). Intellectual enrichment moderated decline in cognitive efficiency (p 5 0.031, h p 2 5 0.126) and memory (p 5 0.037, h p 2 5 0.115), with greater intellectual enrichment protecting against decline. MS disease progression was more negatively associated with change in cognitive efficiency and memory among patients with lower vs higher MLBG and intellectual enrichment. Conclusion: We provide longitudinal support for theories of brain reserve and cognitive reserve in MS. Larger MLBG protects against decline in cognitive efficiency, and greater intellectual enrichment protects against decline in cognitive efficiency and memory. Consideration of these protective factors should improve prediction of future cognitive decline in patients with MS.
Background: The placebo-controlled phase of the PreCISe study showed that glatiramer acetate dela... more Background: The placebo-controlled phase of the PreCISe study showed that glatiramer acetate delayed onset of clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome and brain lesions on MRI. Objective: To compare the effects of early versus delayed glatiramer acetate treatment in the open-label phase of PreCISe. Methods: Patients with a clinically isolated syndrome suggestive of MS with unifocal manifestation and ≥2 T2-weighted brain lesions were randomized to receive glatiramer acetate 20 mg/d (early-treatment, n=198) or placebo (delayed-treatment, n=211) for 36 months or until conversion to CDMS, followed by open-label glatiramer acetate treatment for two years. Results: Early glatiramer acetate treatment reduced CDMS conversion risk by 41% (hazard ratio 0.59, 95% confidence interval 0.44–0.80; p=0.0005) versus delayed-treatment, and was associated with a 972-day delay (185%) in conversion to CDMS, less brain atrophy (−28%, p=0.0209), fewer new...
The recent application of diffusion tensor magnetic resonance imaging (DT MRI) to assess the brai... more The recent application of diffusion tensor magnetic resonance imaging (DT MRI) to assess the brain pathological changes associated to multiple sclerosis (MS) is providing important pieces of information which are improving our understanding of disease pathophysiology [22]. In this context, DT MRI was particularly helpful in confirming that MS-related tissue damage does not only result in focal lesions, but also involves diffusely the normal-appearing white matter (NAWM) and the grey matter (GM) [22].
Objectives: To investigate, using resting state (RS) functional MRI (fMRI), gender‐related differ... more Objectives: To investigate, using resting state (RS) functional MRI (fMRI), gender‐related differences of functional connectivity (FC) and functional network connectivity (FNC) of the human brain. Experimental design: One‐hundred and four young healthy subjects (48/56 men/women), aged between 20 and 29 years, underwent a 10‐min RS fMRI acquisition. Independent component analysis (ICA) and statistical parametric mapping were used to assess gender‐related differences in RSNs, with and without correction for regional gray matter (GM) volume. The relationships among all RSNs was also assessed using a FNC method. Principal observations: For all networks, significant between‐group differences of RS activity were found. Between‐group comparisons of RSNs changed when adjusting for GM volume, as follows: (1) there was only marginal effect on the analysis of sensory (i.e., sensorimotor, visual, and auditory) networks; and (2) there was a significantly increased difference when cognitive netwo...
The assessment of brain volume change with serial MRI provides an objective measure of an importa... more The assessment of brain volume change with serial MRI provides an objective measure of an important component of the pathology of multiple sclerosis. Glatiramer acetate (GA) has a beneficial effect on clinical and MRI measures of disease activity and burden in patients with relapsingremitting (RR) multiple sclerosis. This study investigated the impact of GA treatment on the development of brain atrophy in RR multiple sclerosis patients. The study consisted of a 9-month, double-blind, placebo-controlled phase followed by a 9-month open-label phase. Patients were randomized to receive either 20 mg GA or placebo by daily subcutaneous injections and underwent brain MRI scans every month during the first phase, and every 3 months during the second phase of the study. Using a semi-automated segmentation technique based on local thresholding, brain volume was measured from seven contiguous periventricular slices from the scans obtained at baseline, the end of the double-blind phase and the end of the study. From the original trial cohort, image
To investigate whether additional "occult" tissue changes can be detected in the normal-appearing... more To investigate whether additional "occult" tissue changes can be detected in the normal-appearing white matter and gray matter of otherwise normal elderly individuals with nonspecific white-matter hyperintensities on conventional magnetic resonance images of the brain. Methods: Conventional and magnetization transfer magnetic resonance images were obtained from 12 otherwise normal elderly subjects with white-matter hyperintensities and 11 age-and sex-matched normal individuals. After automatic tissue segmentation, image coregistration, and masking of T2-visible lesions, we obtained magnetization transfer ratio histograms of the normal-appearing white matter and gray matter. For each histogram, the average magnetization transfer ratio, the peak height, and the peak position were measured. We also calculated the percentages of gray-matter and white-matter volumes normalized over the total volume of the intracranial content and the total normalized brain volumes. Results: Average magnetization transfer ratio (P=.03) and mean peak position (P=.01) of the gray-matter histograms from elderly individuals with white-matter hyperintensities were significantly lower than the corresponding quantities from those without white-matter hyperintensities. The normalized percentages of gray and white matter and normalized brain volume did not differ between the 2 groups. The average gray-matter magnetization transfer ratio was correlated with the average lesion magnetization transfer ratio (r=0.68; PϽ.01). Conclusions: This study shows that brain abnormalities in otherwise normal elderly subjects with nonspecific white-matter hyperintensities extend beyond the macroscopic white-matter lesions visualized on conventional magnetic resonance images.
Background: Magnetization transfer magnetic resonance imaging (MT MRI) can provide in vivo marker... more Background: Magnetization transfer magnetic resonance imaging (MT MRI) can provide in vivo markers reflecting the severity of multiple sclerosis-related brain damage occurring within and outside T2-visible lesions. Objective: To investigate the effect of intravenous immunoglobulin (IVIG) treatment on the accumulation of brain damage in patients with secondary progressive multiple sclerosis (SPMS), measured using MT MRI. Design, Patients, and Intervention: Seventy patients with SPMS participating in the European, multicenter, randomized, double-blind, placebo-controlled trial of IVIG in SPMS underwent brain T2-weighted and MT MRI at baseline and after 12 and 24 months. The MT MRI scans were post-processed and analyzed to obtain MT ratio values from T2-visible lesions and MT ratio histograms from the normal-appearing brain tissue (NABT).
Fast fluid-attenuated inversion-recovery (FLAIR) sequences are sensitive for detecting lesions in... more Fast fluid-attenuated inversion-recovery (FLAIR) sequences are sensitive for detecting lesions in patients with multiple sclerosis (MS). More rapid fast-FLAIR imaging of the brain can be achieved by the concomitant use of half-Fourier acquisition single-shot turbo spin-echo (HASTE-FLAIR) and echo-planar imaging (EPI-FLAIR). The present study was performed in a large cohort of subjects to assess and compare the number and volume of brain lesions detected by the fast-FLAIR, HASTE-FLAIR, and EPI-FLAIR sequences in patients with MS. Fast-FLAIR, HASTE-FLAIR, and EPI-FLAIR sequences were obtained from 46 consecutive MS patients. Lesions seen on each type of sequence were counted and classified by consensus by two observers. Lesion volumes were measured using a semiautomated segmentation technique based on local thresholding. The quality of the fast-FLAIR images was significantly better than that of HASTE-FLAIR and EPI-FLAIR images. Fast-FLAIR revealed significantly more lesions and higher...
Neuroborreliosis is frequently indistinguishable from multiple sclerosis (MS) on both clinical an... more Neuroborreliosis is frequently indistinguishable from multiple sclerosis (MS) on both clinical and radiologic grounds. By using MR imaging, we assessed "occult" brain white matter (WM), brain gray matter (GM), and cervical cord damage in patients with neuroborreliosis in an attempt to achieve a more accurate picture of tissue damage in these patients, which might contribute to the diagnostic work-up. We studied 20 patients with neuroborreliosis and 11 sex- and age-matched control subjects. In all subjects, we acquired dual echo, T1-weighted, diffusion tensor (DT) and magnetization transfer (MT) MR imaging scans of the brain and fast short-tau inversion recovery and MT MR imaging scans of the cervical cord. T2-visible lesion load was measured by using a local thresholding segmentation technique. Mean diffusivity and fractional anisotropy histograms of the brain and cervical cord MT ratio histograms were produced. Normalized brain volumes (NBV) were measured by using SIENAx....
Improving the sensitivity of MR imaging for the detection of multiple sclerosis (MS) lesions in t... more Improving the sensitivity of MR imaging for the detection of multiple sclerosis (MS) lesions in the cord might be useful in the diagnostic workup and could lead to a better understanding of the evolution of the disease. The purpose of this study was to compare fast spin-echo (FSE) with magnetization transfer-prepared gradient-echo (MT-GE) and fast short-inversion-time inversion recovery (fast-STIR) MR sequences to determine which is best for imaging cervical cord lesions in MS patients. FSE, MT-GE, and fast-STIR MR images were obtained in 56 MS patients and 10 healthy control subjects with a 1.5-T MR system and a phased-array coil. Cord lesions seen on images obtained with each sequence were counted by two observers in two stages (stage 1: random review of the complete sets of images from each technique; stage 2: side-by-side review with a retrospective count of lesions). At the end of stage 1, a mean of 1.16 cord lesions per patient were seen on FSE images, 1.57 on MT-GE images (35...
We describe the dynamics and the nature of the presymptomatic phase of multiple sclerosis (MS) in... more We describe the dynamics and the nature of the presymptomatic phase of multiple sclerosis (MS) in a patient for whom MR abnormalities suggestive of MS were found before the development of clinical symptoms. The patient was monitored with serial monthly MR imaging of the brain and spinal cord for 5 months. Disease activity during the presymptomatic phase showed imaging characteristics comparable to that of early relapsing-remitting MS in terms of enhancing lesions, duration of enhancement, and new lesions depicted by T2-weighted imaging. Measurements derived from magnetization transfer imaging suggested that the amount and degree of tissue destruction within and outside the lesions revealed by T2-weighted imaging were mild. This, together with the fact that only one of the 43 new lesions that developed during the presymptomatic phase was located in a neurologically eloquent area, may be the reason why, for a relatively long period, the patient had no clinical manifestations of MS des...
Hypointense lesions can be visible on fast fluid-attenuated inversion recovery (FLAIR) MR images ... more Hypointense lesions can be visible on fast fluid-attenuated inversion recovery (FLAIR) MR images of the brain of patients with multiple sclerosis (MS), and they may be produced by severely damaged white matter. To test the role of these lesions as an MR marker of MS severity, we assessed their relationship with clinical findings and other MR measures. Using a 1.5-T scanner, dual-echo rapid acquisition with relaxation enhancement, fast FLAIR, and T1-weighted MR images (24 axial, 5-mm-thick contiguous interleaved sections) were obtained from 50 patients (32 with relapsing-remitting and 18 with secondary progressive MS). Hypointense lesions were visible on the fast FLAIR images of 19 patients (mean number of lesions, 7.8; range 1-22); their median load was 1.4 mL (range, 0.05-12.6 mL). The median lesion load was significantly higher in patients with secondary progressive MS than in those with relapsing-remitting MS on the T1-weighted images. Both the number and the load of hypointense ...
MR imaging is now widely used to monitor disease progression in patients with multiple sclerosis ... more MR imaging is now widely used to monitor disease progression in patients with multiple sclerosis (MS). The purpose of this study was to explore the relationship between disability status and existing and new MR parameters in MS patients. Forty-one patients with clinically definitive MS were studied. MR imaging included T2- and T1-weighted imaging as well as gradient-echo imaging with and without magnetization transfer contrast. We used surface-based thresholding segmentation techniques to obtain T2 and T1 lesion load, T1/T2 ratio, and several magnetization transfer ratio (MTR) lesion load parameters. MTR histographic analysis included measurements of absolute peak height (aHp), relative peak height (rHp), MTR of the peak (MTRp), mean MTR (MTRm), and MTR25, MTR50, and MTR75, relating to the integrals of the histogram at 25%, 50%, and 75%, respectively, of the total area under the curve. All MR parameters were correlated with Expanded Disability Status Scale (EDSS) score, disease dura...
Our goal was to evaluate whether improved spatial resolution of MR images results in the detectio... more Our goal was to evaluate whether improved spatial resolution of MR images results in the detection of higher volumes of hypointense lesions in patients with multiple sclerosis (MS). A magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) sequence with subsequent reconstruction of axial sections with 5-, 3-, and 1-mm thickness and a dual-echo sequence were obtained in 16 patients with relapsing-remitting or secondary-progressive MS. The volumes of MR imaging abnormalities present on each of these studies were measured using a semiautomated segmentation technique based on local thresholding. The hypointense lesion volumes seen on the three reconstructed MP-RAGE sets of images were compared using the Friedman test and correlated with the hyperintense lesion volume on proton density-weighted images and with scores on the Expanded Disability Status Scale using Spearman's rank correlation coefficient. The median volume of hypointense lesions increased from 1.2 mL (range, 0 ...
We describe a case of hereditary congenital mirror movements (MMs) in a 76-year-old man, who afte... more We describe a case of hereditary congenital mirror movements (MMs) in a 76-year-old man, who after an ischemic stroke, had persistence of MMs in the paretic hand during voluntary movements of the contralateral arm. By using functional MR imaging to investigate the performance of motor and sensory tasks with the affected and the unaffected hands, we found evidence for increased ipsilateral primary motor cortex activity and reduced transcallosal inhibition. Both these mechanisms are likely to be involved in the genesis of MMs.
The spinal cord is frequently involved in multiple sclerosis (MS), and cord damage may be an impo... more The spinal cord is frequently involved in multiple sclerosis (MS), and cord damage may be an important contributor to disability. Diffusion tensor magnetic resonance imaging (DT-MRI) provides quantitative information about the structural and orientational features of the central nervous system. In order to assess whether diffusion tensor-derived measures of cord tissue damage are related to clinical disability, mean diffusivity (MD) and fractional anisotropy (FA) histograms from the cervical cord were acquired from a large cohort of MS patients. Diffusion-weighted sensitivity-encoded (SENSE) echo planar images of the cervical cord, and brain dual-echo and diffusion-weighted scans were acquired from 44 patients with MS and 17 healthy controls. Cord and brain MD and FA histograms were produced. An analysis of variance model, adjusting for cord volume and patient age, was used to compare cord DT-MRI parameters from controls and patients. A multivariate linear regression model was used to identify DT-MRI variables independently associated with disability. Average cervical cord FA was significantly lower in MS patients compared to controls. Cord cross-sectional area, average FA and average MD were all significantly correlated with the degree of disability (r values ranging from 0.36 to 0.51). The multivariate linear regression model retained average cord FA and average brain MD as variables independently associated with disability, with a correlation coefficient of 0.73 (P < 0.001). DT-MRI reveals a loss of cervical cord tissue structure in MS patients. The strong correlation found between a composite DT-MRI score and disability suggests that a full and accurate assessment of cervical cord damage in MS provides information that usefully contributes to an explanation of the clinical manifestations of the disease.
Objective: Based on the theories of brain reserve and cognitive reserve, we investigated whether ... more Objective: Based on the theories of brain reserve and cognitive reserve, we investigated whether larger maximal lifetime brain growth (MLBG) and/or greater lifetime intellectual enrichment protect against cognitive decline over time. Methods: Forty patients with multiple sclerosis (MS) underwent baseline and 4.5-year follow-up evaluations of cognitive efficiency (Symbol Digit Modalities Test, Paced Auditory Serial Addition Task) and memory (Selective Reminding Test, Spatial Recall Test). Baseline and follow-up MRIs quantified disease progression: percentage brain volume change (cerebral atrophy), percentage change in T2 lesion volume. MLBG (brain reserve) was estimated with intracranial volume; intellectual enrichment (cognitive reserve) was estimated with vocabulary. We performed repeatedmeasures analyses of covariance to investigate whether larger MLBG and/or greater intellectual enrichment moderate/attenuate cognitive decline over time, controlling for disease progression. Results: Patients with MS declined in cognitive efficiency and memory (p , 0.001). MLBG moderated decline in cognitive efficiency (p 5 0.031, h p 2 5 0.122), with larger MLBG protecting against decline. MLBG did not moderate memory decline (p 5 0.234, h p 2 5 0.039). Intellectual enrichment moderated decline in cognitive efficiency (p 5 0.031, h p 2 5 0.126) and memory (p 5 0.037, h p 2 5 0.115), with greater intellectual enrichment protecting against decline. MS disease progression was more negatively associated with change in cognitive efficiency and memory among patients with lower vs higher MLBG and intellectual enrichment. Conclusion: We provide longitudinal support for theories of brain reserve and cognitive reserve in MS. Larger MLBG protects against decline in cognitive efficiency, and greater intellectual enrichment protects against decline in cognitive efficiency and memory. Consideration of these protective factors should improve prediction of future cognitive decline in patients with MS.
Background: The placebo-controlled phase of the PreCISe study showed that glatiramer acetate dela... more Background: The placebo-controlled phase of the PreCISe study showed that glatiramer acetate delayed onset of clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome and brain lesions on MRI. Objective: To compare the effects of early versus delayed glatiramer acetate treatment in the open-label phase of PreCISe. Methods: Patients with a clinically isolated syndrome suggestive of MS with unifocal manifestation and ≥2 T2-weighted brain lesions were randomized to receive glatiramer acetate 20 mg/d (early-treatment, n=198) or placebo (delayed-treatment, n=211) for 36 months or until conversion to CDMS, followed by open-label glatiramer acetate treatment for two years. Results: Early glatiramer acetate treatment reduced CDMS conversion risk by 41% (hazard ratio 0.59, 95% confidence interval 0.44–0.80; p=0.0005) versus delayed-treatment, and was associated with a 972-day delay (185%) in conversion to CDMS, less brain atrophy (−28%, p=0.0209), fewer new...
The recent application of diffusion tensor magnetic resonance imaging (DT MRI) to assess the brai... more The recent application of diffusion tensor magnetic resonance imaging (DT MRI) to assess the brain pathological changes associated to multiple sclerosis (MS) is providing important pieces of information which are improving our understanding of disease pathophysiology [22]. In this context, DT MRI was particularly helpful in confirming that MS-related tissue damage does not only result in focal lesions, but also involves diffusely the normal-appearing white matter (NAWM) and the grey matter (GM) [22].
Objectives: To investigate, using resting state (RS) functional MRI (fMRI), gender‐related differ... more Objectives: To investigate, using resting state (RS) functional MRI (fMRI), gender‐related differences of functional connectivity (FC) and functional network connectivity (FNC) of the human brain. Experimental design: One‐hundred and four young healthy subjects (48/56 men/women), aged between 20 and 29 years, underwent a 10‐min RS fMRI acquisition. Independent component analysis (ICA) and statistical parametric mapping were used to assess gender‐related differences in RSNs, with and without correction for regional gray matter (GM) volume. The relationships among all RSNs was also assessed using a FNC method. Principal observations: For all networks, significant between‐group differences of RS activity were found. Between‐group comparisons of RSNs changed when adjusting for GM volume, as follows: (1) there was only marginal effect on the analysis of sensory (i.e., sensorimotor, visual, and auditory) networks; and (2) there was a significantly increased difference when cognitive netwo...
The assessment of brain volume change with serial MRI provides an objective measure of an importa... more The assessment of brain volume change with serial MRI provides an objective measure of an important component of the pathology of multiple sclerosis. Glatiramer acetate (GA) has a beneficial effect on clinical and MRI measures of disease activity and burden in patients with relapsingremitting (RR) multiple sclerosis. This study investigated the impact of GA treatment on the development of brain atrophy in RR multiple sclerosis patients. The study consisted of a 9-month, double-blind, placebo-controlled phase followed by a 9-month open-label phase. Patients were randomized to receive either 20 mg GA or placebo by daily subcutaneous injections and underwent brain MRI scans every month during the first phase, and every 3 months during the second phase of the study. Using a semi-automated segmentation technique based on local thresholding, brain volume was measured from seven contiguous periventricular slices from the scans obtained at baseline, the end of the double-blind phase and the end of the study. From the original trial cohort, image
To investigate whether additional "occult" tissue changes can be detected in the normal-appearing... more To investigate whether additional "occult" tissue changes can be detected in the normal-appearing white matter and gray matter of otherwise normal elderly individuals with nonspecific white-matter hyperintensities on conventional magnetic resonance images of the brain. Methods: Conventional and magnetization transfer magnetic resonance images were obtained from 12 otherwise normal elderly subjects with white-matter hyperintensities and 11 age-and sex-matched normal individuals. After automatic tissue segmentation, image coregistration, and masking of T2-visible lesions, we obtained magnetization transfer ratio histograms of the normal-appearing white matter and gray matter. For each histogram, the average magnetization transfer ratio, the peak height, and the peak position were measured. We also calculated the percentages of gray-matter and white-matter volumes normalized over the total volume of the intracranial content and the total normalized brain volumes. Results: Average magnetization transfer ratio (P=.03) and mean peak position (P=.01) of the gray-matter histograms from elderly individuals with white-matter hyperintensities were significantly lower than the corresponding quantities from those without white-matter hyperintensities. The normalized percentages of gray and white matter and normalized brain volume did not differ between the 2 groups. The average gray-matter magnetization transfer ratio was correlated with the average lesion magnetization transfer ratio (r=0.68; PϽ.01). Conclusions: This study shows that brain abnormalities in otherwise normal elderly subjects with nonspecific white-matter hyperintensities extend beyond the macroscopic white-matter lesions visualized on conventional magnetic resonance images.
Background: Magnetization transfer magnetic resonance imaging (MT MRI) can provide in vivo marker... more Background: Magnetization transfer magnetic resonance imaging (MT MRI) can provide in vivo markers reflecting the severity of multiple sclerosis-related brain damage occurring within and outside T2-visible lesions. Objective: To investigate the effect of intravenous immunoglobulin (IVIG) treatment on the accumulation of brain damage in patients with secondary progressive multiple sclerosis (SPMS), measured using MT MRI. Design, Patients, and Intervention: Seventy patients with SPMS participating in the European, multicenter, randomized, double-blind, placebo-controlled trial of IVIG in SPMS underwent brain T2-weighted and MT MRI at baseline and after 12 and 24 months. The MT MRI scans were post-processed and analyzed to obtain MT ratio values from T2-visible lesions and MT ratio histograms from the normal-appearing brain tissue (NABT).
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Papers by Mara Rocca